title: Tolerability of prophylactic aerosolized liposomal amphotericin-B and impact on pulmonary function: data from a randomized placebo-controlled trial.
abstract: BACKGROUND
  Invasive pulmonary aspergillosis (IPA) is a leading cause of mortality in immunocompromised patients, with the highest risk observed in patients with acute leukaemia or lung transplantation. IPA-prophylactic strategies include administration of aerosolized amphotericin-B. Liposomal amphotericin-B (L-AmB) is one of the formulations available, although few data exist on safety and tolerability.
  
  
  METHODS
  Data on tolerability, systemic toxicity and effects of aerosolized L-AmB on pulmonary function were recorded in a subgroup out of 271 haematological patients enrolled in a placebo-controlled trial on the efficacy of aerosolized L-AmB for the prevention of IPA. Using an adaptive aerosol-delivery system, nebulization of L-AmB or placebo was performed during chemotherapy-induced neutropenia for 30 min/day on 2 consecutive days/week with a maximum of 6 weeks.
  
  
  RESULTS
  Thirty-eight patients (41 episodes) received L-AmB, 39 patients (49 episodes) received placebo. Proportions of patients with >20% post-nebulization decline in forced expiratory volume in 1s (FEV(1)) or forced vital capacity (FVC) did not differ between groups. Also 26/38 L-AmB patients (68%) versus 31/39 patients (79%) on placebo had no significant decline during the entire treatment (p=0.20). Coughing was significantly more reported in L-AmB patients (p<0.0001). No differences were observed when baseline and post-nebulization serum levels of renal function and hepatic enzymes were compared.
  
  
  CONCLUSIONS
  Short-term prophylactic nebulization of L-AmB was well tolerated and not associated with decline in pulmonary function or systemic adverse effects.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Erasmus MC, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Lennert
authors.initials: L
authors.lastname: Slobbe
authors.forename: Eric
authors.initials: E
authors.lastname: Boersma
authors.forename: Bart J A
authors.initials: BJ
authors.lastname: Rijnders
mesh_terms: D000328:Adult; D000336:Aerosols / Q000008:administration & dosage*; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects*; D019072:Antibiotic Prophylaxis / Q000009:adverse effects*; D000935:Antifungal Agents / Q000009:adverse effects*; D001228:Aspergillosis / Q000517:prevention & control; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications; D010919:Placebos; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D000336:Aerosols; D000935:Antifungal Agents; D010919:Placebos; C068538:liposomal amphotericin B; D000666:Amphotericin B